Effect of Farxiga on Renal Function and Size in Type 2 Diabetic Patients With Hyperfiltration

Purpose

The investigators propose to treat newly diagnosed, hyperfiltering T2DM patients with or
without microalbuminuria with dapagliflozin or metformin for 4 months. The metformin-treated
group will serve as controls for improved glycemic control, since the investigators have
shown that insulin therapy to normalize A1c reduces hyperfiltration and kidney size in T1DM
patients.

Premenopausal females who are not practicing acceptable contraceptive methods
Participation in another trial with an investigational drug within 30 days Alcohol or
drug abuse within the preceding 6 months

Any condition, psychiatric or medical, which in the opinion of the investigator would
interfere with the successful completion of the study

Estimated glomerular filtration rate <60 mL/min•1.73m2. Patients at risk for volume
depletion due to co-existing conditions or concomitant medications, such as loop
diuretics should have careful monitoring of their volume status

Study Design

Phase

Phase 4

Study Type

Interventional

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary Purpose

Treatment

Masking

None (Open Label)

Arm Groups

Arm

Description

Assigned Intervention

ExperimentalDapagliflozin

Subjects will be randomized to dapagliflozin, 5 mg/day. After 2 weeks (Visit 5), dapagliflozin will be increased to 10 mg/day, Subjects who are taking Metformin at time of randomization we will add Dapagliflozin to current metformin.

Subjects who Drug naïve we will give Metformin- XR, 1000 mg/day. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).Subject who are on metformin at time of randomization we will add Glipizide 5 mg( to be increased to 10 mg at Visit 5), Subject who are on Glipizide at time of randomization we will add Metformin- XR, 1000 mg/day. After 2 weeks (Visit 5), metformin will be increased to 1000 mg bid (twice a day).

Recruiting Locations

More Details

Status

Recruiting

Sponsor

The University of Texas Health Science Center at San Antonio

Study Contact

Detailed Description

Hyperfiltration is a characteristic feature in experimental models of diabetes and is
causally related to an increase in intraglomerular pressure. In newly diagnosed diabetic
patients, both type 1 and type 2, hyperfiltration and enlarged kidney size commonly are
observed, and these hemodynamic/anatomic abnormalities are associated with an increased risk
for the development of diabetic nephropathy.

In poorly controlled diabetic individuals, the filtered load of glucose is markedly increased
and glucose - with sodium - reabsorption by the SGLT2 transporter in the proximal tubule is
augmented. As a consequence sodium delivery to the macula densa is reduced, making the kidney
think that it is under perfused and this results in afferent renal arteriolar vasodilation.
The efferent arteriole of the hyperfiltrating diabetic kidney also is hypersensitive to
angiotensin II despite the absence of systemic RAS activation. The net result of these
hemodynamic changes is an increase in intraglomerular pressure and hyperfiltration. Further,
angiotensin is a potent growth factor and contributes to the increase in size of individual
glomeruli and total kidney size. Since the intraglomerular pressure is related to the radius
(r3) by the Law of LaPlace, the increase in glomerular size also contributes to
hyperfiltration.

Based upon the preceding sequence, it follows that a drug that blocks glucose, along with
sodium, reabsorption in the proximal tubule would enhance sodium delivery to the macula
densa, cause afferent renal arteriolar constriction, reduce intraglomerular
pressure/hyperfiltration, and decrease kidney size. In hyperfiltering diabetic patients with
microalbuminuria, the investigators also would expect the microalbuminuria to decrease.
Consistent with this scenario, animal studies have documented that both acute and chronic
inhibition of SGLT2 decreases hyperfiltration and prevents diabetic nephropathy. A recent
study in hyperfiltering type 1 diabetic patients treated with empagliflozin has provided
additional support for the tubular glomerular feedback hypothesis.

The investigators propose to treat newly diagnosed, hyperfiltering T2DM patients with or
without microalbuminuria with dapagliflozin or metformin for 4 months. The metformin-treated
group will serve as controls for improved glycemic control, since the investigators have
shown that insulin therapy to normalize A1c reduces hyperfiltration and kidney size in T1DM
patients

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health).
The listing of studies provided is not certain to be all studies for which you might be eligible.
Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.

This study (NCT02911792) was last processed and updated on 5/8/2020 by ClinicalTrials.gov.